©2005 Lee Bardwell

Pedigree

Analysis

Autosomal vs. sex-linked traits

• Autosomal traits are caused by genes on autosomes (chrms #1- #22)– e.g., we speak of autosomal recessive or

autosomal dominant traits or diseases

• Sex-linked traits are caused by genes on the sex chrms (X or Y) – e.g., we speak of X-linked recessive or X-

linked dominant traits or diseases

©2004 Lee Bardwell

Dominant inheritance

• If D is the disease allele and d is normal, then only dd genotypes are disease free*

• Dominant trait/disease found in every generation*

• Affected kid never** born to unaffected parents

**Assuming no new mutation*Assuming 100% penetrance

Recessive inheritance

• If d is the disease allele and D is normal, then only dd genotypes are affected

• typically not seen in every generation

•Affected kid can be born to unaffected parents

X-linked recessive inheritance

•Rules for recessive inheritance apply

•Mostly males are affected

X-linked dominant inheritance

•Rules for dominant inheritance apply

•Dad’s pass disease to all of their daughters and none of their sons

X-linked genes (and X-linked diseases)...

• Males: haploid (= hemizygous) for most X-linked genes.

• --> men are more frequently affected by diseases caused recessive alleles of X-linked genes

©2001 Lee Bardwell

Female carrier* mates with normal male

FXNXN

Y

XN

XA

• Half* her daughters will be carriers

• Half* her sons will be affected

F x MXNXA XNY

Eggs

Sperm

XN

MXNY

normal normal

MXAY

affected

FXAXN

carrier

©2001 Lee Bardwell`*on average

*of x-linked recess. disease

Affected male* mates with normal female

Y

XN

XN

• All his daughters will be carriers

• None of his sons will be affected

F x MXNXN XAY

Eggs

Sperm

XA

MXNY

normal

MXNY

normal

FXNXA

carrier

FXNXA

carrier

©2001 Lee Bardwell

*with x-linked recess. disease

Some X-linked recessive human diseases

• Hemophilia A• Hemophilia B• Red-green color blindness• Duchenne muscular dystrophy• Retinitis pigmentosum (one of many

loci) • Lesch-Nyhan Syndrome• Many others

©2000 Lee Bardwell

No need to memorize

Affected male mates with normal female

Y

XN

XN

• All his daughters will be affected

• None of his sons will be affected

F x MXNXN XAY

Eggs

Sperm

XA

MXNY

normal

MXNY

normal

FXNXA

affected

FXNXA

affected

©2001 Lee Bardwell

X-linked dominant disease

Affected female mates with normal male

Y

XN

XA

• _______of her daughters will be _______

• _______of her sons will be ____________

F x MXNXA XNY

Eggs

Sperm

XN

©2005 Lee Bardwell`

X-linked dominant disease

Work this outfor yourself

Some X-linked dominant human diseases

• Incontinentia Pigmenti • Hypophosphatemic Rickets• Charcot-Marie-Tooth disease• Chondrodysplasia Punctata

©2005 Lee Bardwell

No need to memorize

Pedigree Analysis

NormalFemale

NormalMale

Mating

1st born

Siblings

Affected

©2001 Lee Bardwell

I

II

See H&J pp. 52-53

Fig. 2.17. Conventional symbols used in depicting human pedigrees.

Warning:

I

II

III

IV

Pedigree showing X-linked recessive inheritance

©2002 Lee Bardwell

I

II

III

IV

Could this be autosomal recessive?

©2002 Lee Bardwell

I

II

III

IV

Could this be X-linked dominant?

©2002 Lee Bardwell

I

II

III

IV

Could this be autosomal dominant?

©2002 Lee Bardwell

©2001 Lee Bardwell

If two affected parents have an unaffected kid, recessiveness* can

be ruled out

*both autosomal and x-linked

(assuming 100% penetrance)

©2001 Lee Bardwell

If unaffected parents have an affected kid, dominance* can be

ruled out

*both autosomal and x-linked

©2000 Lee Bardwell

If unaffected parents have an affected daughter, dominance and x-linked recessive can be

ruled out

©2001 Lee Bardwell

If affected woman has unaffected son, or unaffected man has affected

daughter, x-linked recessive can be ruled out

NOT XR NOT XR

If unaffected woman has affected son, or affected man has unaffected

daughter, x-linked dominant can be ruled out

XD XD©2001 Lee Bardwell

Fig. 2.18. Inheritance of dominant gene

for Huntington disease

Inheritance of dominant trait

Could this be autosomal recessive?

Genetic Counseling

©2000,2005Lee Bardwell

A woman’s brother died from Tay Sach’s Disease (autosomal recessive, lethal), but she is unaffected. What are the chances that she is a carrier of the

disease?

A.2/3 (67%) B. 1/2 (50%) C. 1/4 (25%)D. 1/6 (17%) E. 1/8 (12.5%)

Hint

©2000,2005Lee Bardwell

A woman’s brother died from Tay Sach’s Disease (autosomal recessive, lethal), but she is unaffected. What are the chances that she is a carrier of the

disease?

A.2/3 (67%) B. 1/2 (50%) C. 1/4 (25%)D. 1/6 (17%) E. 1/8 (12.5%)

©2005 Lee Bardwell

DC

A BD

d

D d

DD

Dd dd

Dd

A.2/3 (67%) B. 1/2 (50%) C. 1/4 (25%)D. 1/6 (17%) E. 1/8 (12.5%)

The answer is…

Problem 2

Assuming your grandfather is a carrier (heterozygote) for a rare recessive, disease causing allele of a given gene, What’s the chance that you are also a carrier of this allele?

©2001 Lee Bardwell

you

©2001,2005 Lee Bardwell

D E

F G

H

IF

THEN ?

A.2/3 B. 1/2 C. 1/4 D. 1/6 E.1/8

1/2 (50% chance) momgot the allele

1/2 (50% chance) she gaveit to you if she had it

1/2 x 1/2 = 1/4

= Chance that you got a given allele from Grandpa D

©2000 Lee Bardwell

D E

F G

H

Problem 3Your grandfather’s sister had cystic fibrosis (rare, autosomal recessive). That’s the only case in your family.(A) What’s the chance that you are a carrier of CF?

©2001 Lee Bardwell

A.2/3 B. 1/2 C. 1/4 D. 1/6 E.1/8

you©2001 Lee Bardwell

D E

F G

C

H

A B

Your grandfather’s sister had CF but he, his parents, and his descendants are unaffected, as are those who married into the family

A. 2/3B. 1/2C. 1/4 D. 1/6E. 1/8

you©2001 Lee Bardwell

D E

F G

C

H

A BD

d

D d

DD

Dd dd

Dd

2/3

you

©2001 Lee Bardwell

D E

F G

H

IF

THEN ?

ANSWERSA. 1/4 = Chance that you got any particular allele

from from grandpa

B. 1/6 = correct answer = 1/4 (see A) x 2/3 (chances that grandpa was a carrier)

©2001 Lee Bardwell